(a) Field of the Invention
The present invention relates to a composition for nucleic acid delivery and a method for preparing the same, more particularly to a composition for nucleic acid delivery, which has excellent stability in the body environment and excellent intracellular nucleic acid delivery efficiency, and is capable of target directed delivery of nucleic acid, and a method for preparing the same.
(b) Description of the Related Art
Recently, industrial importances of small interfering ribonucleic acid (siRNA), antisense oligonucleic acids, plasmid deoxyribonucleic acid, and the like as nucleic acid-based drugs are highlighted. However, to develop nucleic acids as drugs, efficient delivery to cells or tissues should be solved first.
For intracellular delivery of nucleic acids, studies on viral vectors or non-viral vectors using polymer or nanoparticles are under progress. Among them, a viral vector has higher gene delivery efficiency than a non-viral vector, but its application to humans is very limited due to safety problem of using virus. Thus, development of non-viral vectors as a safer alternative to viral vectors is under progress.
Currently, cationic liposome, TAT peptide, or cationic polymer such as polyethylenimine (PEI) is largely used as delivery system for nucleic acid, particularly siRNA. Particularly, it has been reported that cationic polymer of polyethyleneimine (PEI) compresses negatively charged nucleic acids to form colloidal particles, and holds pH buffering capacity even in lysosome in the cells, and thus, delivers plasmid deoxyribonucleic acids to various cells (Boussif et al., Proc. Natl. Acad. Sci. USA 92 (1995) 7297-7301; Godbey et al., J. Controlled Release 60 (1999)149-160).
However, it was found that the cationic polymer causes cell aggregation in the body and binds electrostatically to blood protein to lower siRNA activity, and causes fatal toxicity to body organs such as liver, lung, and the like. Thus, it is known that the cationic polymer is difficult to be utilized alone as siRNA delivery system. And, regarding the use of polyethyleneimine, there are remaining problems relating to intracellular gene delivery efficiency and cytotoxicity, and thus, many studies for solving these problems are under progress. For example, to reduce cytotoxicity of polyethyleneimine (PEI), a method of modification with dextran sulfate, human serum albumin, polyethylene glycol, and the like has been attempted, but the modified PEIs commonly exhibited lower gene delivery efficiency than PEI itself.
Accordingly, there is a need for technology of efficient intracellular delivery of small interfering ribonucleic acid, oligonucleic acid such as antisense oligonucleic acid, and the like, having excellent stability in the body.
Meanwhile, gold nanoparticles are known to have excellent biocompatibility, and the particle size may be controlled and the surface modification is easy, and thus, many studies on binding biomolecules to them are under progress. And, hyaluronic acid is linear polymer polysaccharide consisting of alternating β-D-N-acetylglucosamine and β-D-glucuronic acid, it does not have species- and organ-specificity, and it is known to exhibit excellent biocompatibility even when implanted or injected in the body.